Scientists have found more than 100 new genes that can cause cancer if they become mutated. The discovery was part of the largest survey of the human genome to date, which also suggests that the number of cancer genes is far larger than previously thought.

All cancers are thought to be caused by DNA mutations in specific genes. "Thus far, there are approximately 350 genes in the human genome that have been shown to be cancer genes," said Mike Stratton, co-leader of the Cancer Genome Project at the Wellcome Trust Sanger Institute, Cambridge. "This is from a full spec of around 25,000 genes in the human genome."

The cancer genes have been painstakingly identified during more than 25 years of research. But new technology is speeding up the process, allowing scientists to systematically identify all the genes in a cancer cell. These gene sequences can then be compared to healthy cells to identify differences in DNA.

Prof Stratton's team looked at a family of 500 genes that include protein kinases, molecules that act like switches. "This set of genes is known to regulate key functions in virtually all cell processes, growth, differentiation, telling cells to live and die," said Andrew Futreal of the Sanger Institute.

Mutations in some of these genes are already implicated in cancer. An example is the Braf gene - a mutation here is found in more than 60% of cases of the skin cancer malignant melanoma.

In the new study, researchers looked at more than 500 genes in about 200 samples of different types of cancer. The results, published today in Nature, showed about 1,000 mutations in the protein kinase genes of cancer cells. "We find evidence for approximately 100 new cancer genes - this is a larger number than we really expected to find," said Prof Stratton.

Based on previous research, Dr Futreal said he had only expected to find about 10 new cancer genes in their sample. The 1,000 mutations were classified in two categories: drivers and passengers. Driver mutations are the ones that cause cancer cells to grow whereas passengers make no contribution to cancers.

"It turns out that most mutations in cancers are passengers. However, buried among them are much larger numbers of driver mutations than anticipated. This suggests that many more genes contribute to cancer development than was thought," said Dr Futreal. The challenge in the future will be differentiating between driver and passenger mutations.

Another surprise was the way in which the mutations were spread among the cancers - in some samples, scientists found large numbers of mutations in a pattern they had never seen before. "The number and patterns of these mutations are an archaeological signature of something that has happened to that cancer in the past, something that has been implicated in its causation," said Prof Stratton.

Some of these causes, such as the drug a cancer has been treated with, ultraviolet light and cigarette smoke, can already be interpreted. But Prof Stratton said the new mutations would need further research to explain. "This must be telling us something about previous exposures, perhaps to environmental chemicals and also abnormalities of DNA repair in these cancers."